Abstract. The recent advances in induced pluripotent stem cells (iPSCs) and gene therapy tools have opened up a new avenue to study and treat diseases, particularly of disorders with defective bone marrow. Bone marrow failure syndromes are usually marked with depleted blood cells caused due to dysfunctional bone marrow compartment. Fanconi anemia (FA) is one such bone marrow failure syndrome where cellular reprogramming is inefficient, owing to interference of the disease-related genes. To overcome this limitation, it is necessary to fundamentally correct the abnormal gene (e.g.: FANCD1) during or prior to the reprogramming process. In the past, obtaining genetically modified iPSC from the fibroblasts of these patients typically involved multiple steps. But recent progress in the field has paved way for simultaneous reprogramming and gene targeting in a single step using multiple episomal vectors. In this study we propose to take the multiple vector-single step procedure to single vector-single step approach to obtain corrected iPSC from FA fibroblasts. Our single vector is based on a non-integrating negative strand RNA virus, Measles virus (MV). The central hypothesis is that a MV vectors can be designed to express all components in one genome, and lead to the generation of clinically safe, corrected and functional iPSCs from FA fibroblasts. The rationale for the proposed research is that the ?one-cycle? MV vector, MV4F, expressing the four reprogramming factors, generate iPSC from human fibroblasts and is quickly diluted and eliminated from the iPSC after reprogramming. Guided by strong preliminary data, the specific aim of this particular application is to produce a one-cycle ?all-in-one? MV vectors, containing the four reprogramming factors plus Cas9-gRNA, and setup the protocol for concurrently reprogram and edit the genome of human fibroblasts carrying a genetic mutation. The proposed work is innovative, because it capitalizes on a new technology that relies on one single vector expressing the four reprogramming factors (RFs) for the reprogramming of somatic cells into iPSC; and our group developed that technology. Finally, the corrected iPSC will be tested for there ability to differentiated into hematopoietic stem cells. The proposed work is significant because develop a new single vector for the production corrected iPSC, that will be eliminated quickly form the established iPSC and that can be translated into the clinic quickly, as it based on the safe measles vaccine strain. Finally, the proposed research is relevant to that part of NIH's mission that pertains to develop new treatments for Inherited Bone Marrow failure syndromes, haemoglobinopathies, immunodeficiencies, and other monogenetic disorders to reduce the burden of human disease.